The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: a cross-sectional study conducted in Japan

Naoki Saji, Kenta Murotani, Takayoshi Hisada, Tsuyoshi Tsuduki, Taiki Sugimoto, Ai Kimura, Shumpei Niida, Kenji Toba, Takashi Sakurai, Naoki Saji, Kenta Murotani, Takayoshi Hisada, Tsuyoshi Tsuduki, Taiki Sugimoto, Ai Kimura, Shumpei Niida, Kenji Toba, Takashi Sakurai

Abstract

Recent studies have revealed an association between the dysregulation of the gut microbiome and dementia. However, whether this dysregulation is associated with mild cognitive impairment (MCI), an early stage of cognitive decline, in patients without dementia remains unclear. We performed a cross-sectional analysis to determine the association between the gut microbiome and MCI. Data, including patient demographics, risk factors, cognitive function, and brain imaging, were collected. The gut microbiome was assessed through terminal restriction fragment length polymorphism analysis. Multivariable logistic regression models were used to identify factors independently associated with MCI. Graphical modelling was used to illustrate mutual associations between MCI and identified factors. We analysed 82 patients, 61 of whom exhibited MCI. Patients with MCI had a higher prevalence of Bacteroides. Furthermore, patients with more Bacteroides were more likely to present with white matter hyperintensity and high voxel-based specific regional analysis system for Alzheimer's Disease (VSRAD) scores, indicating cortical and hippocampal atrophy. A multivariable logistic regression analysis revealed that a greater prevalence of Bacteroides was independently associated with MCI. Graphical modelling also showed a close association between Bacteroides and MCI. In conclusion, an increased prevalence of Bacteroides is independently associated with the presence of MCI in patients without dementia.

Conflict of interest statement

N.S. has received grants from the NARO Bio-oriented Technology Research Advancement Institution project (Advanced Integration Research for Agriculture and Interdisciplinary Fields) and the BMS/Pfizer Japan Thrombosis Investigator Initiated Research Program. N.S., S.N. and T.S. have received research grants from the Research Funding of Longevity Sciences from the National Center for Geriatrics and Gerontology. N.S., K.T. and T.S. have received research funds for Comprehensive Research on Aging and Health from the Japan Agency for Medical Research and Development (AMED). T.T. has received grants from the NARO Bio-oriented Technology Research Advancement Institution project (Advanced Integration Research for Agriculture and Interdisciplinary Fields).

Figures

Figure 1
Figure 1
Graphical modelling of factors used for the multivariable analyses. Line thickness is proportional to the number of patients that contributed to the comparison. Green lines indicate a positive relationship, and red lines indicate a negative relationship. Abbreviations: mci, mild cognitive impairment; apo, apolipoprotein E ε4 carrier; wmh, white matter hyperintensity; en1, enterotype I; age, patient’s age; smk, smoking habit; cmb, cerebral microbleeds.

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